OBJECTIVES: The aim of the present study is to provide information on clinical outcome of the patients affected by HCV-positive mixed cryoglobulinemia (MC) treated with PEG-IFN and Ribavirin for 6 or 12 months according to the HCV genotype. METHODS: Eighty-six patients (42 women and 44 men) were enrolled in 8 Italian centres. All the patients had MC in the active phase of the disease. The patients received Peginterferon alfa-2b 1.5 mcg/kg/once a week (QW) and daily oral Ribavirin (800/1,000/1,200) according to their body weight for 48 weeks for genotype 1 and 4 and for 24 weeks for genotypes 2 and 3. RESULTS: In the 44 patients who underwent 12 months of therapy, 17 cases (39%) could be considered as 'non-responders' and 11 relapsed, therefore only 16 patients (36%) obtained a sustained virological response. In the 42 patients who underwent six months of therapy only 7 cases (17%) could be considered as 'non-responders' and 8 relapsed, therefore 27 patients (64%) obtained a sustained virological response. Purpura score dropped in both group (p<5.79 x 10-17) and only 5 cases of the group A (11%) and 5 of the group B (12%) did not show any improvement. Arthralgias showed a similar behaviour. Many patients relapsed after the end of the treatment. CONCLUSIONS: This study documents a lower response rate than that observed in the clinical trials with HCV chronic hepatitis, but the presence of comorbidities and older age should be taken into consideration. Most patients (88.5%) showed a complete and persistent recovery from clinical symptoms.